Masaaki Chiku

Unblinded Pilot Study of Autologous Transplantation of Bone Marrow Mononuclear Cells in Patients With Thromboangiitis Obliterans

Background— The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans. Methods and Results— Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684±549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1±0.7 to 1.5±1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year. Conclusions— In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.

Plaque Morphology at Coronary Sites With Focal Spasm in Variant Angina

In the present study, the intravascular ultrasound (IVUS) morphologic appearance of coronary atherosclerotic plaque associated with focal spasm was prospectively studied in 45 patients with or without focal coronary spasm provoked by ergonovine or acetylcholine. The percent plaque area and plaque arc were determined from the IVUS images at the sites of spasm. Calcified lesion was defined as the presence of high-intensity echo with acoustic shadowing. Twenty-three patients had focal coronary spasm defined as angiographic narrowing >75% and IVUS demonstrated atherosclerotic plaque in these 23 sites. In the 22 patients without focal spasm, IVUS demonstrated 18 atherosclerotic lesions in 17 patients and the remaining 5 patients did not have significant lesions. There was no difference in the percent plaque area and plaque arc between plaque lesions with (47+/-10%, 298+/-71 degrees ) and without (39+/-15%, 249+/-83 degrees ) coronary spasm. Interestingly, calcified lesion was less frequently present at the sites with than at those without spasm (p<0.05). These results indicate that the presence of plaque without calcification is likely to be related to the occurrence of focal vasospasm, although the severity and distribution of the disease did not differ between each patient group.

Miglitol improves postprandial endothelial dysfunction in patients with acute coronary syndrome and new-onset postprandial hyperglycemia

BackgroundHyperglycemia, a risk factor for development of cardiovascular disease, causes endothelial dysfunction. Alpha-glucosidase inhibitors (α-GIs) improve postprandial hyperglycemia (PPHG) and may have favorable effects on associated cardiovascular disease. Effects of α-GIs in patients with acute coronary syndrome (ACS) and PPHG remain unclear; thus, we assessed the effect of α-GI miglitol on endothelial function in such patients by digital reactive hyperemia peripheral arterial tonometry (RH-PAT).MethodsFifty-four patients with ACS who underwent primary percutaneous coronary intervention were enrolled in the study: 36 with new-onset PPHG and 18 with normal glucose tolerance. Eighteen PPHG patients were given 50 mg of miglitol with each meal for 1 week. Endothelial function was assessed on the basis of the RH-PAT index (RHI) before and after the 1-week miglitol treatment. The other 18 PPHG patients and the 18 NGT patients were not given any anti-diabetic agent for 1 week, and endothelial function was assessed.ResultsPostprandial RHI decreased significantly in patients with PPHG. Miglitol improved PPHG significantly; postprandial RHI also improved (p = 0.007). Significant inverse correlation was found between the postprandial change in RHI and postprandial fasting-to-60-minutes surge in glucose (r = -0.382, p = 0.009). Moreover, the improvement in endothelial function correlated with the reduced postprandial glucose surge achieved with miglitol (r = -0.462, p = 0.001).ConclusionsPostprandial changes in glucose are related to endothelial dysfunction in ACS. Miglitol-based improvement in PPHG appears to improve endothelial function. The effect of miglitol on glucose-dependent endothelial function might improve outcomes of ACS.

Clinical utility of negative contrast intravascular ultrasound to evaluate plaque morphology before and after coronary interventions

Although intravascular ultrasound (IVUS) is used for evaluation of plaque volume and lumen size as well as detection of vessel wall structures after catheter-based interventions, differentiation between the lumen and plaque structures can be difficult. This study attempted to evaluate the efficacy of negative contrast IVUS imaging for assessment of vessel wall morphology after coronary interventions. IVUS studies were performed in 67 lesions in 66 patients before and after coronary interventions. After the baseline ultrasound imaging run, warm 5% glucose solution was injected manually through the guiding catheter into the coronary artery to washout blood from the lumen to avoid speckled reflections from red blood cells (negative contrast). Quantitative measurements were obtained and plaque morphology was assessed for the presence and extent of medial dissections and intimal flaps. There was no difference in each quantitative parameter between baseline images and negative contrast images. The vessel wall boundary was clearly delineated from the lumen, which was defined as effective negative contrast in 51 of 67 lesions (76%). The baseline images revealed plaque dissection in 9 lesions (18%) and an intimal flap in 13 lesions (25%). In addition, 4 dissections (8%) and 16 intimal flaps (31%) were visualized during the infusion of negative contrast. Additional treatment was performed in 4 lesions (8%) based on the images with negative contrast. Negative contrast IVUS was more sensitive in demonstrating a plaque fracture than were baseline images. This method is useful for enhancing the diagnostic capability of IVUS imaging and may influence the decision-making process during interventional procedures.

Current use of direct oral anticoagulants for atrial fibrillation in Japan: Findings from the SAKURA AF Registry

Large‐scale investigations on the use of oral anticoagulants including direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) have not included Japanese patients.

MDCT of the anomalous origin of the right coronary artery from the left sinus of Valsalva associated with bicuspid aortic valve

Anomalous origin of the right coronary artery is a relatively rare coronary artery anomaly which is known to cause myocardial ischemia and sudden death. Association of anomalous origin of the right coronary artery with congenital bicuspid aortic valve is even rarer with only a few cases being reported previously. We describe, for the first time, MDCT findings of anomalous origin of the right coronary artery associated with congenital bicuspid aortic valve.

Detection of coronary artery disease by free-breathing, whole heart coronary magnetic resonance angiography: our initial experience

Free-breathing, whole heart coronary magnetic resonance angiography (MRA) has gained great attention as a totally noninvasive diagnostic modality for the detection of coronary artery disease. We examined the accuracy of coronary MRA to identify the presence or absence of coronary artery stenosis in comparison with conventional coronary angiography. Free-breathing, whole heart coronary MRA was performed in 43 consecutive patients undergoing conventional coronary angiography. A total of 172 coronary arteries and 344 coronary artery segments were analyzed. In the coronary artery segment-based analysis, the sensitivity to detect coronary stenosis ≥50% was 82% and specificity was 100%. The accuracy, positive predictive value, and negative predictive value was 97%, 98%, and 96%, respectively. In the vessel-based analysis the sensitivity was 86%, specificity 99%, accuracy 95%, positive predictive value 98%, and negative predictive value 94%. In the patient-based analysis, the sensitivity to detect coronary stenosis <50% was 97% and the specificity to define luminal narrowing <50% was 90%. The accuracy, positive predictive value, and negative predictive value was 95%, 97%, and 90%, respectively. Free-breathing, whole heart coronary MRA yields excellent diagnostic accuracy to detect significant coronary artery disease and has the potential to become the routine diagnostic modality for patients with suspected coronary artery disease.

Acute anterior myocardial infarction superimposing double left anterior descending artery: Depiction at whole-heart coronary magnetic resonance angiography

Double left anterior descending artery arising from the left and right coronary arteries is an extremely rare congenital coronary anomaly. We describe a patient with anterior myocardial infarction, in whom whole-heart coronary magnetic resonance angiography detected double left anterior descending artery.

A Novel Micro-Angiography Detecting Angiogenesis, Application for Autologous Bone Marrow Mononuclear Cells Transplantation in the Patients with Critical Limb Ischemia

Conventional Anigiographic Findings in Autologous Bone Marrow Mononuclear Cells Transplantation for Critical Limb Ischemia: Bone marrow mononuclear cells have many of the characteristics of stem cells for mesenchymal tissues, and secrete many angiogenic cytokines. We performed autologous transplantation of bone marrow mononuclear cells in six patients with critical limb ischemia due to Buerger disease, who were not candidates for catheter or surgical revascularization. Leg pains at rest and skin ulcers improved after bone marrow transplantation in all patients, although significant collateral developments after the therapy by conventional angiography could not be observed. Autologous transplantation of bone marrow mononuclear cells including stem cells improved critical limb ischemia due to Buerger disease. Neovascularization after therapeutic angiogenesis might be quite small and could not be visualized by conventional angiography.